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Biomedical subjects

R Conklin

Publications and source records attributed to R Conklin.

18 recordsLinked to original sources

A comparison of the effects of isoproterenol and forskolin on immunologic and nonimmunologic release of histamine from guinea-pig superfused trachea and dispersed tracheal cells.

This study has compared the abilities of isoproterenol and forskolin to inhibit immunologic- and nonimmunologic-induced histamine release from guinea-pig superfused trachea and enzymatically dispersed tracheal cells. Contraction was also measured in the former preparation. The potency of isoproterenol was similar for inhibition of all parameters associated with immunologic (ovalbumin) challenge in the two preparations. In contrast, forskolin appeared less potent in inhibiting ovalbumin-induced histamine release from dispersed tracheal cells. Histamine release by the nonimmunologic secretagogues d-tubocurarine and compound 48/80 was not altered by either substance. However, inhibition by isoproterenol and forskolin of tracheal contraction was evident when challenge was conducted with d-tubocurarine and compound 48/80. Inhibition of contraction appears to be a result of functional antagonism at the level of the smooth muscle. The superfused trachea is a useful preparation in which to explore the effects of substances that modulate mast cell mediator release.

Animals

Pharmacologic modulation of the influence of the epithelium on immunologic- and nonimmunologic-induced histamine release and contraction in guinea pig superfused tracheal strips.

The influence of the epithelium on contractions and histamine release evoked by ovalbumin and d-tubocurarine has been examined in guinea pig superfused tracheal strips under several experimental conditions. Without drug pretreatment, removal of the epithelium resulted in larger (P < .05) total histamine released by ovalbumin, 10(-4) to 10(-1) mg/ml, and by d-tubocurarine, 3 x 10(-3) M. In the presence of indomethacin, 5 x 10(-6) M, epithelium removal resulted in elevated histamine release only at smaller ovalbumin concentrations, 10(-4) and 10(-3) mg/ml. Indomethacin did not change the influence of the epithelium on histamine release by d-tubocurarine. Indomethacin treatment abolished the influence of the epithelium on ovalbumin-induced tracheal contraction. With indomethacin, larger (P < .05) histamine release was seen with ovalbumin, 10(-1) and 1 mg/ml, when the epithelium was intact. The larger histamine release in response to ovalbumin, 10(-1) mg/ml, in the presence of the epithelium was unaltered by pyrilamine, 10(-6) M, cimetidine, 10(-4) M, and thioperamide, 10(-6) M, to block histamine H1, H2 and H3 receptors, respectively. Therefore, histamine released by ovalbumin does not stimulate histamine release through an action on these receptors when the epithelium is intact. In the presence, but not in the absence, of the epithelium, A64077, 10(-5) M, and ICI198615, 10(-8) and 10(-6) M, inhibitors of 5-lipoxygenase and LTD4/E4 receptors, respectively, inhibited histamine release by ovalbumin, 10(-1) mg/ml. Histamine release by ovalbumin, 10(-4) mg/ml, and d-tubocurarine, 3 x 10(-3) M, studied with or without epithelium was not altered by A64077 or ICI198615.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Studies of desensitization and cross-desensitization to immunologic and nonimmunologic stimuli that evoke contraction and histamine release in superfused guinea pig trachea.

This study examined the possibility that there is cross-desensitization between immunologic and nonimmunologic stimuli that evoke contraction and histamine release (HR) in the isolated guinea pig trachea. Compound 48/80 and D-tubocurarine were found to cause homologous and heterologous desensitization for both contraction and HR from superfused trachea. Specific antigen challenge of trachea obtained from animals sensitized with either IgG1 (ovalbumin [OA]) or IgE (oxazalone-human serum albumin [OX-HSA]) also resulted in homologous desensitization for both contraction and HR. However, in experiments with animals sensitized with both IgG1 and IgE antibodies, prechallenge with OA resulted in cross-desensitization to OX-HSA, whereas the reverse sequence was ineffective in eliciting this phenomenon. This may be related to the type of desensitization produced by each antigen (specific versus nonspecific) or to heterogeneity of mast cells in the tissue. Prechallenge of the trachea with compound 48/80 or D-tubocurarine failed to alter subsequent effects of antigen after active sensitization with OA or passive sensitization with either IgG1 or IgE antibodies. Small but statistically significant decreases in tracheal responses to D-tubocurarine were observed after antigen prechallenge to active both IgG1 and IgE antibodies. This is the first study to demonstrate a cross-desensitization between compound 48/80 and D-tubocurarine and the first to examine cross-desensitization with IgG1 and IgE antibodies in the guinea pig trachea. The overall conclusion is that there is no major overlap in the desensitization mechanisms between immunologic and nonimmunologic stimuli in the guinea pig trachea.

Animals

Transplantation of adrenal medullary tissue to caudate nucleus using stereotactic techniques.

Stereotactic techniques were used to transplant adrenal medullary tissue to the head of the right caudate nucleus in 12 patients with Parkinson's disease. No significant lasting complications were seen. All patients had an initial improvement. 11 of the 12 patients remain improved over their preoperative condition after 6-18 months, 3 with good results and 9 with only modest improvement. At 6 months, the mean Schwab and England score had improved from 59.2 +/- 18.8 preoperatively to 75.8 +/- 15.1 (p less than or equal to 0.01) and the mean Hoehn and Yahr scale had improved from 3.42 +/- 0.90 to 2.92 +/- 0.63 (p less than or equal to 0.01).

Adrenal Medulla

Flow cytometric analysis of megakaryocytes from patients with abnormal platelet counts.

Megakaryocytes (MKs) from 40 patients with quantitative platelet disorders and 19 normal volunteers were analyzed by flow cytometry for size, fine cell internal structure and granularity, membrane expression of the glycoprotein (GP) IIb/IIIa complex, and for ploidy distribution. Analysis was performed on unfractionated minimally manipulated marrows obtained from routine bone marrow aspirates. MKs were labeled with a fluorescent lineage-specific monoclonal antibody to the GPIIb/IIIa complex followed by DNA staining with propidium iodide. Eight hundred to 3,000 MKs were analyzed in each sample. The modal ploidy distribution in normals was 16N, comprising about half of the megakaryocytic population, with 22.6% of the cells less than or equal to 8N and 22.0% greater than or equal to 32N. Twelve thrombocytopenic patients with decreased marrow MKs on biopsy (mean platelet count [MPC] 44,600/microliters) showed an increase in low ploidy cells with 53.2% less than or equal to 8N (P less than .01); cell size was reduced in three patients when compared to normal cells of identical ploidy (P less than .05). Eight thrombocytopenic patients with enhanced platelet destruction (with normal or increased MKs on biopsy and shortened platelet survival; MPC 41,400/microliters) showed an increased proportion of high ploidy cells greater than or equal to 32N to 39.2% (P less than .01). Increased cell size and granularity were found in four of these patients (P less than .05). Six patients with thrombocytopenia secondary to multiple mechanisms affecting both platelet production and destruction (MPC 66,700/microliters) showed no shift in ploidy. Four patients with primary thrombocytosis (two with thrombocythemia and two with polycythemia vera; MPC 822,500/microliters) showed a marked shift toward high ploidy cells with 42.3% greater than or equal to 32N and 7.6% greater than or equal to 64N cells (P less than .01). The shift was accompanied by a marked increase in cell size and granularity in the patients with thrombocythemia. Ten patients with thrombocytosis secondary to chronic blood loss, malignant or inflammatory disorders (MPC 714,000/microliters), showed variable distributions with four patients exhibiting a shift in ploidy to the right similar to that found in the patients with increased platelet destruction. Based upon the present data, flow cytometric ploidy distribution may be diagnostically useful in thrombocytopenic patients by discriminating between disorders of platelet production and destruction. (ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow

Renal function studies during intravenous acyclovir treatment of immune suppressed patients including renal transplantation.

We assessed the effect of acyclovir therapy on renal function during a course of therapy for herpesvirus disease. Renal function was assessed by measuring the clearances of inulin, albumin, and beta 2-microglobulin at the beginning and end of acyclovir therapy. Thirty-two patients had valid paired inulin clearances and 21 had valid paired albumin and beta 2-microglobulin clearances. No significant mean decrement of renal function was observed; however, 2 patients had a reversible renal dysfunction associated with acyclovir therapy which disappeared soon after discontinuation of the drug and was unassociated with a prior or recurrent renal dysfunction in short-term follow-up.

Acyclovir

Rotavirus antibody in chickens as measured by enzyme-linked immunosorbent blocking assay.

The antibody titer of 202 chickens to SA-11 rotavirus was determined by enzyme-linked immunosorbent blocking assay. The chickens were from 15 separate flocks on six farms. The titer was detectable (1:18 or greater dilution) in 43% of the chickens. The wide variation in infection rate between flocks on individual farms (0% to 90%) indicated there is probably not significant transmission of the virus between flocks on the farm. Significant differences in numbers of serotest-positive birds were found between separate farms, possibly reflecting different management practices.

Animals

Clinical classification of plasma cell myeloma.

Clinical and electrophoretic data were evaluated in 334 consecutive patients with myeloma or monoclonal peaks on serum or urine electrophoresis. Of the 242 patients with myeloma, 7% had localized plasmacytomas with absent or low level monoclonal peaks on electrophoresis and received only radiotherapy to focal disease areas. Chemotherapy was also withheld from eight other patients in an indolent clinical phase of multiple myeloma. Disease progression was apparent in about one third of the patients with localized and indolent myeloma within 12 months. Forty-three patients had idiopathic peaks on serum electrophoresis; more than 90% were of the IgG type with levels less than 3.0 gm/100 ml. Serial elecrtophoreses, immunoglobulin quantitations, and skeletal radiographs are recommended for the evaluation of patients with idiopathic peaks, the classification of early phases of myeloma, and the confirmation of tumor mass change.

Bence Jones Protein